The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data ...about rivaroxaban use in routine clinical practice are needed.
XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007.
Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 95% CI 0·54-1·54, p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 95% CI 0·24-1·07, p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 36·0% of 2619 in the rivaroxaban group vs 805 37·5% of 2149 in the standard anticoagulation group).
In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings.
Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.
Abstract Background Data on left atrial/left atrial appendage (LA/LAA) thrombus resolution after nonvitamin K antagonist (VKA) oral anticoagulant (NOAC) treatment are scarce. The primary objective of ...X-TRA was to explore the use of rivaroxaban for the resolution of LA/LAA thrombi in patients with nonvalvular atrial fibrillation (AF) or atrial flutter, with the CLOT-AF registry providing retrospective data after standard-of-care therapy in this setting. Methods X-TRA was a prospective, single-arm, open-label, multicenter study that investigated rivaroxaban treatment for 6 weeks for LA/LAA thrombus resolution in patients with nonvalvular AF or atrial flutter and LA/LAA thrombus confirmed at baseline on a transesophageal echocardiogram (TEE). CLOT-AF retrospectively collected thrombus-related patient outcome data after standard-of-care anticoagulant treatment for 3–12 weeks in patients with nonvalvular AF or atrial flutter who had LA/LAA thrombi on TEE recorded in their medical file. Results In X-TRA, patients were predominantly (95.0%) from Eastern European countries. The adjudicated thrombus resolution rate was 41.5% (22/53 modified intention-to-treat mITT patients; 95% confidence interval CI 28.1-55.9%) based on central TEE assessments. Resolved or reduced thrombus was evident in 60.4% (32/53 mITT patients; 95% CI 46.0-73.6%) of patients. In CLOT-AF, the reported thrombus resolution rate was 62.5% (60/96 mITT patients; 95% CI 52.0-72.2%), and appeared better in Western European countries (34/50; 68.0%) than Eastern European countries (26/46; 56.5%). Conclusion X-TRA is the first prospective, multicenter study examining LA/LAA thrombus resolution with a NOAC in VKA-naïve patients or in patients with suboptimal VKA therapy. Rivaroxaban could be a potential option for the treatment of LA/LAA thrombi.
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This trial compared standard therapy (dual antiplatelet therapy plus a vitamin K antagonist) with two regimens containing rivaroxaban plus antiplatelet therapy. The rivaroxaban groups had reduced ...rates of bleeding and similar efficacy in preventing cardiovascular events.
Approximately 5 to 8% of patients who undergo percutaneous coronary intervention (PCI) have atrial fibrillation.
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Dual antiplatelet therapy (DAPT) with a P2Y
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inhibitor and aspirin is superior to oral anticoagulation with a vitamin K antagonist in reducing the risk of thrombosis in patients undergoing placement of a first-generation stent,
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but oral anticoagulation is superior to DAPT in reducing the risk of ischemic stroke in patients with atrial fibrillation.
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The treatment strategy for patients with atrial fibrillation who have received stents must balance the risk of stent thrombosis and ischemic stroke with the risk of bleeding. A common guideline-supported . . .
Background Guidelines recommendations regarding anticoagulant therapy after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on retrospective, nonrandomized ...observational data. Currently, patients are treated with triple-therapy (dual antiplatelet therapy DAPT + oral anticoagulation therapy), but neither the duration of DAPT nor the level of anticoagulation has been studied in a randomized fashion. Recent studies also suggest dual pathway therapy with clopidogrel plus oral anticoagulation therapy may be superior, and other studies suggest that novel oral anticoagulants such as rivaroxaban may further improve patient outcomes. Design PIONEER AF-PCI ( ClinicalTrials.gov NCT01830543) is an exploratory, open-label, randomized, multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and 1 vitamin K antagonist (VKA) treatment strategy in subjects who have paroxysmal, persistent, or permanent nonvalvular AF and have undergone PCI with stent placement. Approximately 2,100 subjects will be randomized in a 1:1:1 ratio to receive either rivaroxaban 15 mg once daily plus clopidogrel 75 mg daily for 12 months (a WOEST trial–like strategy), or rivaroxaban 2.5 mg twice daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, an ATLAS trial–like strategy), or dose-adjusted VKA once daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, traditional triple therapy). All patients will be followed up for 12 months for the primary composite end point of Thrombolysis in Myocardial Infarction major bleeding, bleeding requiring medical attention, and minor bleeding (collectively, clinically significant bleeding). Conclusion The PIONEER AF-PCI study is the first randomized comparison of VKA vs novel oral anticoagulant therapy in patients with NVAF receiving antiplatelet therapy after PCI to assess the relative risks of bleeding complications.
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Limited data are available on the characteristics, clinical management, and outcomes of patients with atrial fibrillation at risk of stroke, from a worldwide perspective. The aim of this study was to ...describe the baseline characteristics and initial therapeutic management of patients with non-valvular atrial fibrillation across the spectrum of sites at which these patients are treated.
The Global Anticoagulant Registry in the FIELD (GARFIELD) is an observational study of patients newly diagnosed with non-valvular atrial fibrillation. Enrollment into Cohort 1 (of 5) took place between December 2009 and October 2011 at 540 sites in 19 countries in Europe, Asia-Pacific, Central/South America, and Canada. Investigator sites are representative of the distribution of atrial fibrillation care settings in each country. Cohort 1 comprised 10,614 adults (≥18 years) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks, with ≥1 investigator-defined stroke risk factor (not limited to those in existing risk-stratification schemes), and regardless of therapy. Data collected at baseline included demographics, medical history, care setting, nature of atrial fibrillation, and treatments initiated at diagnosis. The mean (SD) age of the population was 70.2 (11.2) years; 43.2% were women. Mean±SD CHADS2 score was 1.9±1.2, and 57.2% had a score ≥2. Mean CHA2DS2-VASc score was 3.2±1.6, and 8,957 (84.4%) had a score ≥2. Overall, 38.0% of patients with a CHADS2 score ≥2 did not receive anticoagulant therapy, whereas 42.5% of those at low risk (score 0) received anticoagulant therapy.
These contemporary observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke.
ClinicalTrials.gov TRI08888.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Rivaroxaban demonstrated superior efficacy and a similar safety profile to enoxaparin for the prevention of venous thromboembolism in the phase III RECORD programme in patients undergoing ...elective hip or knee replacement surgery. The XAMOS study investigated adverse events, including bleeding and thromboembolic events, in patients receiving rivaroxaban for thromboprophylaxis in routine clinical practice. XAMOS was a non-interventional, open-label cohort study in patients undergoing major orthopaedic surgery of the hip or knee (predominantly elective arthroplasty), in which rivaroxaban was compared with other pharmacological thromboprophylaxis. All adverse events were documented, including symptomatic thromboembolic and bleeding events. Crude and adjusted incidences based on propensity score subclasses were calculated and compared between the rivaroxaban and standard-of-care groups. A total of 17,701 patients were enrolled from 252 centres in 37 countries. Crude incidences of symptomatic thromboembolic events three months after surgery in the safety population were 0.89% in the rivaroxaban group (n=8,778) and 1.35% in the standard-of-care group (n=8,635; odds ratio OR 0.65; 95% confidence interval CI 0.49–0.87), and 0.91% and 1.31% (weighted) in the propensity score-adjusted analysis (OR 0.69; 95% CI 0.56–0.85), respectively. Treatment-emergent major bleeding events (as defined in the RECORD studies) occurred in 0.40% and 0.34% of patients in the rivaroxaban and standard-of-care groups in the safety population (OR 1.19; 95% CI 0.73–1.95), and in 0.44% versus 0.33% (weighted) in the propensity score-adjusted analysis (OR 1.35; 95% CI 0.94–1.93), respectively. This study in unselected patients confirmed the favourable benefit–risk profile of rivaroxaban seen in the RECORD programme.
The antiarrhythmic drug dronedarone was compared with placebo in 4628 patients with atrial fibrillation. At a mean follow-up of 21 months, the rate of first hospitalization due to cardiovascular ...events or death was significantly lower with dronedarone than with placebo. The dronedarone group had higher rates of bradycardia, QT-interval prolongation, nausea, diarrhea, rash, and increase in the serum creatinine level.
The antiarrhythmic drug dronedarone was compared with placebo in patients with atrial fibrillation. At a mean follow-up of 21 months, the rate of first hospitalization due to cardiovascular events or death was significantly lower with dronedarone.
Atrial fibrillation is the most common type of cardiac arrhythmia requiring medical care, with a prevalence of almost 1% in the adult population in the United States.
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Its prevalence increases with age, affecting 3.8% of the U.S. population over 60 years of age and 9.0% of the population older than 80 years. Over the past two decades, hospitalizations for atrial fibrillation in the United States have increased by a factor of two to three, resulting in a substantial public health burden.
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Despite advances in nonpharmacologic therapy,
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many symptomatic patients receive medical treatment for rhythm control. Currently available antiarrhythmic agents are . . .
Background: Non-vitamin K antagonist oral anticoagulants including rivaroxaban are widely used for stroke prevention in patients with atrial fibrillation (AF). We investigated the relationship ...between plasma biomarkers (indicative of thrombogenesis, fibrinolysis and inflammation) and left atrial thrombus resolution after rivaroxaban treatment.
Methods: This was an ancillary analysis of the X-TRA study, which was a prospective interventional study evaluating the use of rivaroxaban for left atrial/left atrial appendage (LA/LAA) thrombus resolution in AF patients. We assessed various biomarkers of thrombogenesis/fibrinolysis D-dimer, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1 + 2 (F1,2), thrombin-antithrombin (TAT) complexes, von Willebrand factor (vWF) and inflammation high-sensitivity interleukin-6 (hsIL-6), and high-sensitivity C-reactive protein (hsCRP), measured at baseline and after 6 weeks' of rivaroxaban treatment.
Results: There was a significant decrease in the mean levels of hsCRP, D-dimer, vWF, and TAT from baseline to end of treatment with rivaroxaban. Although none of the thrombogenesis/fibrinolysis biomarkers showed a significant relationship with thrombus resolution, high inflammatory biomarkers at baseline were significantly associated with an increased chance of the thrombus being completely resolved (hsIL-6) or reduced/resolved (hsCRP).
Conclusions: Biomarkers of inflammation are significantly associated with LA/LAA thrombus outcomes in AF patients prospectively treated with rivaroxaban.
Changes in the thrombogenesis/fibrinolysis biomarker levels reflected the expected pharmacodynamics of rivaroxaban.
Higher levels of inflammation biomarkers were significantly associated with thrombus being completely resolved or reduced.
In atrial fibrillation (AF), lower risks of death and bleeding with non-vitamin-K oral anticoagulants (NOACs) were reported in meta-analyses of controlled trials, but whether these findings hold true ...in real-world practice remains uncertain. Risks of bleeding and death were assessed in 52 032 patients with newly diagnosed AF enrolled in GARFIELD-AF (Global Anticoagulant Registry in the FIELD–Atrial Fibrillation), a worldwide prospective registry. Baseline treatment was vitamin K antagonists (VKAs) with or without antiplatelet (AP) agents (VKA ± AP) (20 151; 39.3%), NOACs ± AP agents (14 103; 27.5%), AP agents only (10 748; 21.0%), or no antithrombotics (6219; 12.1%). One-year follow-up event rates (95% confidence interval CI) of minor, clinically relevant nonmajor (CRNM), and major bleedings were 2.29 (2.16-2.43), 1.10 (1.01-1.20), and 1.31 (1.21-1.41) per 100 patient-years, respectively. Bleeding risk was lower with NOACs than VKAs for any bleeding (hazard ratio (HR) 95% CI), 0.85 0.73-0.98) or major bleeding (0.79 0.60-1.04). Compared with no bleeding, the risk of death was higher with minor bleeding (adjusted HR aHR, 1.53 1.07-2.19), CRNM bleeding (aHR, 2.59 1.80-3.73), and major bleeding (aHR, 8.24 6.76-10.04). The all-cause mortality rate was lower with NOACs than with VKAs (aHR, 0.73 0.62-0.85). Forty-five percent (114) of all deaths occurred within 30 days, and 40% of these were from intracranial/intraspinal hemorrhage (ICH). The rates of any bleeding and all-cause death were lower with NOACs than with VKAs. Major bleeding was associated with the highest risk of death. CRNM bleeding and minor bleeding were associated with a higher risk of death compared to no bleeding. Death within 30 days after a major bleed was most frequently related to ICH. This trial was registered at www.clinicaltrials.gov as #NCT01090362.
•Use of NOACs rather than VKAs was associated with lower risks of all-cause death and all bleeding categories in AF patients.•Rate of death was highest in patients with major bleeding and higher in patients with nonmajor bleeding than in those with no bleeding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There are still many unresolved issues concerning patient outcomes and prognostic factors in patients with atrial fibrillation (AF) and left atrial/left atrial appendage (LA/LAA) thrombi. Rivaroxaban ...(Xarelto®), a potent and highly selective oral, direct factor Xa inhibitor, is a new therapeutic option in this setting. The planned study program will consist of a prospective interventional study (X-TRA) and a retrospective observational registry (CLOT-AF). The primary objective of the X-TRA study is to explore the efficacy of rivaroxaban in the treatment of LA/LAA thrombi in patients with nonvalvular AF or atrial flutter, scheduled to undergo cardioversion or AF ablation, in whom an LA/LAA thrombus has been found on transesophageal echocardiography (TEE) before the procedure. The primary end point is the complete LA/LAA thrombus resolution rate at 6 weeks of end of treatment confirmed by TEE. The secondary objectives are to describe categories of thrombus outcome in patients (resolved, reduced, unchanged, larger, or new) confirmed on TEE at the end of treatment (after 6 weeks of treatment), incidence of the composite of stroke and noncentral nervous system systemic embolism at the end of treatment and during follow-up, and incidence of all bleeding at the end of treatment and during follow-up. The objective of the CLOT-AF registry is to provide retrospective thrombus-related patient outcome data after standard-of-care anticoagulant treatment in patients with nonvalvular AF or atrial flutter, who have TEE-documented LA/LAA thrombi. The data will be used as a reference for the prospective X-TRA study. In conclusion, X-TRA and CLOT-AF will provide some answers to the many unresolved issues concerning patient outcomes and prognostic factors in patients with AF and LAA thrombi. Results from this study program would provide the first prospective interventional study (X-TRA) and a large international retrospective observational registry (CLOT-AF) on the prevalence and natural history of LA/LAA thrombi. Unique data on clot resolution with rivaroxaban in a prospective cohort would be obtained in X-TRA.
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